US2623885A - Compounds of the cyclopentanopolyhydrophenanthrene series and process ofmaking same - Google Patents
Compounds of the cyclopentanopolyhydrophenanthrene series and process ofmaking same Download PDFInfo
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- US2623885A US2623885A US126054A US12605449A US2623885A US 2623885 A US2623885 A US 2623885A US 126054 A US126054 A US 126054A US 12605449 A US12605449 A US 12605449A US 2623885 A US2623885 A US 2623885A
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- 150000001875 compounds Chemical class 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 6
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- 150000001241 acetals Chemical class 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 14
- -1 lithium-aluminum hydride Chemical compound 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 150000002084 enol ethers Chemical class 0.000 description 8
- OEOFQABUOAWYMP-UHFFFAOYSA-N oxiren-2-ol Chemical compound OC1=CO1 OEOFQABUOAWYMP-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical group N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical group O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical class CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- This invention relates to the preparation of compounds of the cyclopentanopolyhydrophenanthrene series by reduction of'redu'cible substituents of compounds of the said series with lithium-aluminum hydride, in which process a 3- ositioned a:;8-uns aturated keto-grouping present is not hydrogenated.
- A'further object of this mvention is the preparation of new compounds of the cyclopentanopolyhydrophenanthrene series, such as, for ex ample A -3-keto-22-hydroxy-bisnor cholenes.
- inc-unsaturated 3-ketones of the cyclopentanopolyhydrophenanthrene series are temporarily converted into their enol ethers or cyclic acetals for protection of the 3qpositioned keto group and treated, for thepurpiose of reduction of reducible substituents, with lithium-aluminum hydride.
- Suitable enol ethers are those of the aliphatic, alicyclic or ar aliphatic series; in partioular alkyl ethers are employed, as for example, methyl, ethyl or propyl ethers.
- the enol ethers of A -3-leto;bisnor-cholenic acidand its acid derivatives primarily their esters, suchias the methyl ester, and also the 3-enol ethers of A -3:1'7-androstend ione.
- the 1,2-dio1s or the correspondiug-alkylene oxides in the presence ofan acid catalyst are used.
- the reduction is advantageously carried out in the presence of an indifferent solvent in which the lithium-aluminum hydride is soluble, in partlcular in the presence of ether, or also of tetrahydrofurane, butyl ether or benzene or of mixtures of such diluents, such as in the presence of a mixture of ether and benzene.
- The-enol ethers or cyclic acetals of hydnoxyketonesor amino-ketones obtained in the course of this process can be hydrolyzed in the customary manner in order to produce the corresponding ketones.
- ketones obtained are in part known and in part constitute new compounds. Some of them merit application as therapeutic media.
- the ketones may also be employed as intermediate products for the manufacture of therapeutically valuable compounds.
- Example 1 10 parts of the ethyl enol ether of the methyl ester of M-B-keto-bisnor-cholenic-acid aredissolved in 200 parts by volume of dry ether and slowly added, with exclusion of moisture, to a well stirred mixture of 2.5 parts of lithiumaluminum hydride in 200 parts by volume of dry ether. Thereupon the solution produced is further stirred for 15 minutes and then first carefully treated with parts by volume of water and 1'70 parts by volume of 10 per cent. sulfuric acid. The ethereal solution is then washed with water, dried and evaporated. The crude enol ether of A -3-keto-22hydroxy-bisnorcholene thus obtained, when recrystallized from ethanol, melts unsharply at 125-144 C.
- Example 2 2 parts of the 3-ethyl enol ether of A -3:17- androstendi'one are dissolved in 200 parts by volume of dry ether and slowly added, with exclusion of moisture, to a well stirred mixture of 0.5 part of lithium-aluminum hydride in parts for example, the methyl by volume of dry ether. The solution produced is further stirred for 15 minutes and thereupon carefully treated, with 20 parts by volume of water and 40 :parts by volume of 10 per cent. sulfuric acid. The ethereal solution is then washed with water, dried and evaporated.
- the crude enol ether of A -3ketol7-hydroxy-androstene is, without further purification, dissolved in 100 parts by volume of alcohol and the solution treated with 10 parts by volume of ZN-hydrochloric acid and allowed to stand for 24 hours.
- the solution is thereupon evaporated in vacuum and in this manner the crude A -3-keto-17-hydroxyandrostene (testosterone) obtained, which can be purified in the customary manner.
- Example 3 10 parts of the 3-.ethyl enol ether of A pregnene-17fiol-3-one-21-acid methyl ester are dissolved in 250 parts by volume of dry ether and slowly added, with exclusion of moisture, to a well stirred mixture f 2.5 parts of lithium-aluminum hydride in 200 parts by volume of dry ether. The solution produced is further stirred for 15-20 minutes and-thereupon carefully treated with 100 parts by volume .of water and 17 0, parts by volume of sulfuric :acid of 10 per cent. strength. The ethereal solutionis then washed with water, dried and evaporated.
- the crude ethyl enol ether of A -pregnene-1-7p,21-diol-3-one thus obtained is dissolved in 250 parts by volume of methanol and the solution treated with parts by volume of ZN-aqueous hydrochloric acid and allowed to stand at room temperature for 1 2 days.
- the solution is thereupon evaporated in vacuum and taken up in chloroform.
- the chloroform solu tion is washed with water, .dried and evaporated.
- the residue produces A pregnene-17;9,21-diol-3-one of melting point 243-246 C.
- the ethyl enol ether of M-pregnene-l'Zfl-ol-3- one-21-acid methyl'ester, used as starting material, is obtained from A -androstene-3,17-dione- 3-.ethyl enol ether by condensation with bromo acetic acid ester and zincsaccording tothe method of Reformatzky.
- Example 4 A solution-of 2"p'arts of theB-ethy'l enol ether of A -pregn'adiene-3-one 2l acid-methyl ester in 200 parts -by volume of dry tetrahydro'furane is added, with exclusion of moisture, to a well stirred mixture of 2.5 parts of lithium-aluminum hydride and. 200*:pa'rts by volume of dry tetrahydrofurane. Stirring is "continued for another '1'0-20minutes hydrochloric acid and whereupon 20 parts by volume of water, then 180 parts by volume of sulfuric acid of 10 per cent. strength and finally ether are added gradually.
- the starting material in the above example namely the 3-ethyl enol ether of A -pregnadiene-3-one-2l-acid-methyl ester, is obtained from the 3-enol ether of A -androstene-3,17-dione by condensation with bromo acetic acid ester and zinc according to the method of Reformatzky,and
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Patented Dec. 30, 1952 POLYHYDROPHEN AND PROCESS1OF Karl Miescher, Riehen,
Basel, ceutical Products,
rial No. 126,054. 1948 This invention relates to the preparation of compounds of the cyclopentanopolyhydrophenanthrene series by reduction of'redu'cible substituents of compounds of the said series with lithium-aluminum hydride, in which process a 3- ositioned a:;8-uns aturated keto-grouping present is not hydrogenated.-
A'further object of this mventionis the preparation of new compounds of the cyclopentanopolyhydrophenanthrene series, such as, for ex ample A -3-keto-22-hydroxy-bisnor cholenes.
According to the present invention inc-unsaturated 3-ketones of the cyclopentanopolyhydrophenanthrene series are temporarily converted into their enol ethers or cyclic acetals for protection of the 3qpositioned keto group and treated, for thepurpiose of reduction of reducible substituents, with lithium-aluminum hydride.
The (rm-unsaturated ketones of the cyclowhich pentanopolyhydrophemanthrene senies, contain as reducible substituents for example, a keto, aldehyde, free or esterified'carboxyl, an acid chloride, acid anhydride, acid amide or nitro group, may be converted into any convenient enol ether or cyclic acetal. Suitable enol ethers: are those of the aliphatic, alicyclic or ar aliphatic series; in partioular alkyl ethers are employed, as for example, methyl, ethyl or propyl ethers. There may be particularly mentioned the enol ethers of A -3-leto;bisnor-cholenic acidand its acid derivatives, primarily their esters, suchias the methyl ester, and also the 3-enol ethers of A -3:1'7-androstend ione. In the manufacture of the cyclic aicetals of these particularly of the ethylene glycol, there are used the 1,2-dio1s or the correspondiug-alkylene oxides in the presence ofan acid catalyst. ,g
The reduction is advantageously carried out in the presence of an indifferent solvent in which the lithium-aluminum hydride is soluble, in partlcular in the presence of ether, or also of tetrahydrofurane, butyl ether or benzene or of mixtures of such diluents, such as in the presence of a mixture of ether and benzene.
The-enol ethers or cyclic acetals of hydnoxyketonesor amino-ketones obtained in the course of this process can be hydrolyzed in the customary manner in order to produce the corresponding ketones.
The ketones obtained are in part known and in part constitute new compounds. Some of them merit application as therapeutic media. The ketones may also be employed as intermediate products for the manufacture of therapeutically valuable compounds.
starting materials,
2 Claims. (Cl. 260-3974) AN THRENE SERIES MAKING SAME and Charles Meystre,
Switzerland, assignors to Ciba Pharma- Inc., Summit, N.
No Drawing. I Application November 7, 1949, Se-
In Switzerland November 17,
The following examples illustrate the invention, the parts being by weight unless otherwise stated and the relationship between parts by weight and partsby volume being the same as that between the kilogram and liter:
Example 1 10 parts of the ethyl enol ether of the methyl ester of M-B-keto-bisnor-cholenic-acid aredissolved in 200 parts by volume of dry ether and slowly added, with exclusion of moisture, to a well stirred mixture of 2.5 parts of lithiumaluminum hydride in 200 parts by volume of dry ether. Thereupon the solution produced is further stirred for 15 minutes and then first carefully treated with parts by volume of water and 1'70 parts by volume of 10 per cent. sulfuric acid. The ethereal solution is then washed with water, dried and evaporated. The crude enol ether of A -3-keto-22hydroxy-bisnorcholene thus obtained, when recrystallized from ethanol, melts unsharply at 125-144 C.
are obtained.
For the manufacture of the enol ether Ternn e 1t v ed t 9 ester of A -SB-hydroxy-bisnor-cholenic acid is first oxidized according to Oppenauer with cyclohexanone in the presence of aluminum isopropylate in toluene. The methyl ester of A -3-keto-bisnor-cholenio acid thus obtained, which when recrystallized from acetone melts at l83-184= C., is then converted in the customary manner with orthoformic acid ethyl ester in acidified ethanol solution into the corresponding ethyl enol ether, which when recrystallized from methanol melts at 103-106" C.
Example 2 2 parts of the 3-ethyl enol ether of A -3:17- androstendi'one are dissolved in 200 parts by volume of dry ether and slowly added, with exclusion of moisture, to a well stirred mixture of 0.5 part of lithium-aluminum hydride in parts for example, the methyl by volume of dry ether. The solution produced is further stirred for 15 minutes and thereupon carefully treated, with 20 parts by volume of water and 40 :parts by volume of 10 per cent. sulfuric acid. The ethereal solution is then washed with water, dried and evaporated. The crude enol ether of A -3ketol7-hydroxy-androstene is, without further purification, dissolved in 100 parts by volume of alcohol and the solution treated with 10 parts by volume of ZN-hydrochloric acid and allowed to stand for 24 hours. The solution is thereupon evaporated in vacuum and in this manner the crude A -3-keto-17-hydroxyandrostene (testosterone) obtained, which can be purified in the customary manner. For example, from diluted acetone, needles are obtained of melting point 152-153 C. ([a]D =+l09 in ethanol).
Example 3 .10 parts of the 3-.ethyl enol ether of A pregnene-17fiol-3-one-21-acid methyl ester are dissolved in 250 parts by volume of dry ether and slowly added, with exclusion of moisture, to a well stirred mixture f 2.5 parts of lithium-aluminum hydride in 200 parts by volume of dry ether. The solution produced is further stirred for 15-20 minutes and-thereupon carefully treated with 100 parts by volume .of water and 17 0, parts by volume of sulfuric :acid of 10 per cent. strength. The ethereal solutionis then washed with water, dried and evaporated. The crude ethyl enol ether of A -pregnene-1-7p,21-diol-3-one thus obtained is dissolved in 250 parts by volume of methanol and the solution treated with parts by volume of ZN-aqueous hydrochloric acid and allowed to stand at room temperature for 1 2 days. The solution is thereupon evaporated in vacuum and taken up in chloroform. The chloroform solu tion is washed with water, .dried and evaporated. Upon recrystallization from a mixture of isopropylether hexane, the residue produces A pregnene-17;9,21-diol-3-one of melting point 243-246 C.
The ethyl enol ether of M-pregnene-l'Zfl-ol-3- one-21-acid methyl'ester, used as starting material, is obtained from A -androstene-3,17-dione- 3-.ethyl enol ether by condensation with bromo acetic acid ester and zincsaccording tothe method of Reformatzky.
Example 4 A solution-of 2"p'arts of theB-ethy'l enol ether of A -pregn'adiene-3-one 2l acid-methyl ester in 200 parts -by volume of dry tetrahydro'furane is added, with exclusion of moisture, to a well stirred mixture of 2.5 parts of lithium-aluminum hydride and. 200*:pa'rts by volume of dry tetrahydrofurane. Stirring is "continued for another '1'0-20minutes hydrochloric acid and whereupon 20 parts by volume of water, then 180 parts by volume of sulfuric acid of 10 per cent. strength and finally ether are added gradually.
The ethereal solution is then washed'with water,
dried and evaporated. The crude ethyl enol ether of A -pregnadiene-21-ol-3-one obtained is dissolved in 200.parts by volume of ethanol and the solution-treated with 20 parts by volume of 2N- allowed to stand at room temperature for vv1-2 days. upon evaporated in vacuum and the crude A pregnadiene-21-ol-3-one obtained purified in the customary manner. Upon crystallization from acetone-methanol it melts at -137 C.
The starting material in the above example, namely the 3-ethyl enol ether of A -pregnadiene-3-one-2l-acid-methyl ester, is obtained from the 3-enol ether of A -androstene-3,17-dione by condensation with bromo acetic acid ester and zinc according to the method of Reformatzky,and
KARL MLESCHER. CHARLES MEYSTRE.
REFERENCES CITED The following references are of record in the file of this :patent:
UNITED STATES PATENTS Number Name "Date 2,166,877 Re-ichstein July 18,1939 2,183,589 Reichs"teitl 'Dec. 19, 193.9 2,294,433 WBStbhal Sept. 1, 1942 2,324,522 Loge'mann July 20, 1943 2,356,154 Fernholz Aug. 22, 1944 2,462,133
The solution is there-
Claims (1)
1. PROCESS FOR THE REDUCTION OF COMPOUNDS OF THE CYCLOPENTANOPOLYHYDROPHENATHRENE SERIES, WHICH COMPRISES TREATING A MEMBER OF THE GROUP CONSISTING OF $4-3-KETO-BISNOR-CHLOENIC ACID AND $4-3-KETO-BISNOR-CHOLENIC ACID DERIVATIVES IN THE FORM OF A MEMBER OF THE GROUP CONSISTING OF 3ENOL-ETHERS AND 3-CYCLIC ACETALS WITH LITHIUMALUMINUM HYDRIDE AND HYDROLYZING THE SO FORMED REACTION PRODUCT, WHEREBY $4-3-KETO-22-HYDROXYBISNOR-CHOLENE IS OBTAINED.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2623885X | 1948-11-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2623885A true US2623885A (en) | 1952-12-30 |
Family
ID=4570646
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US126054A Expired - Lifetime US2623885A (en) | 1948-11-17 | 1949-11-07 | Compounds of the cyclopentanopolyhydrophenanthrene series and process ofmaking same |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2623885A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2753342A (en) * | 1953-10-16 | 1956-07-03 | Syntex Sa | Cyclopentanophenanthrene compounds and method for the production thereof |
| US2758993A (en) * | 1954-06-02 | 1956-08-14 | Upjohn Co | Steroid production |
| US2802825A (en) * | 1952-06-28 | 1957-08-13 | Jr Hyp J Dauben | Cyclopentanophenanthrene compounds and process for the production thereof |
| US2806030A (en) * | 1954-03-20 | 1957-09-10 | Syntex Sa | Cyclopentanophenanthrene derivatives and process for the preparation thereof |
| US2824871A (en) * | 1951-11-29 | 1958-02-25 | Upjohn Co | Steroid compounds and process |
| US2842557A (en) * | 1954-08-04 | 1958-07-08 | Merck & Co Inc | Dodecahydrophenanthrene compounds and methods of preparing the same |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2166877A (en) * | 1937-09-28 | 1939-07-18 | Roche Organon Inc | Cortical hormones |
| US2183489A (en) * | 1937-06-09 | 1939-12-12 | Gen Aniline Works Inc | Monoazo dyestuffs |
| US2294433A (en) * | 1937-10-05 | 1942-09-01 | Schering Corp | Hydroxy ketones of the cyclopentanopolyhydrophenanthrene series and method of producing the same |
| US2324522A (en) * | 1939-01-06 | 1943-07-20 | Schering Corp | Process for the manufacture of ketones of the cyclopentano polyhydrophenanthrene series |
| US2356154A (en) * | 1941-08-19 | 1944-08-22 | Squibb & Sons Inc | Cyclic ketals of 3-keto-17-oxy-cythrenes and method of preparing 3-keto-17-oxy-cythrenes |
| US2462133A (en) * | 1945-07-14 | 1949-02-22 | Merck & Co Inc | Process of treating pregnene compounds |
-
1949
- 1949-11-07 US US126054A patent/US2623885A/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2183489A (en) * | 1937-06-09 | 1939-12-12 | Gen Aniline Works Inc | Monoazo dyestuffs |
| US2166877A (en) * | 1937-09-28 | 1939-07-18 | Roche Organon Inc | Cortical hormones |
| US2294433A (en) * | 1937-10-05 | 1942-09-01 | Schering Corp | Hydroxy ketones of the cyclopentanopolyhydrophenanthrene series and method of producing the same |
| US2324522A (en) * | 1939-01-06 | 1943-07-20 | Schering Corp | Process for the manufacture of ketones of the cyclopentano polyhydrophenanthrene series |
| US2356154A (en) * | 1941-08-19 | 1944-08-22 | Squibb & Sons Inc | Cyclic ketals of 3-keto-17-oxy-cythrenes and method of preparing 3-keto-17-oxy-cythrenes |
| US2462133A (en) * | 1945-07-14 | 1949-02-22 | Merck & Co Inc | Process of treating pregnene compounds |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2824871A (en) * | 1951-11-29 | 1958-02-25 | Upjohn Co | Steroid compounds and process |
| US2802825A (en) * | 1952-06-28 | 1957-08-13 | Jr Hyp J Dauben | Cyclopentanophenanthrene compounds and process for the production thereof |
| US2753342A (en) * | 1953-10-16 | 1956-07-03 | Syntex Sa | Cyclopentanophenanthrene compounds and method for the production thereof |
| US2806030A (en) * | 1954-03-20 | 1957-09-10 | Syntex Sa | Cyclopentanophenanthrene derivatives and process for the preparation thereof |
| US2758993A (en) * | 1954-06-02 | 1956-08-14 | Upjohn Co | Steroid production |
| US2842557A (en) * | 1954-08-04 | 1958-07-08 | Merck & Co Inc | Dodecahydrophenanthrene compounds and methods of preparing the same |
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